Acronym Definition
NMYC National Manpower and Youth Council
NMyC National Military Youth Corps
NMyC National Movement for the Youth of Cameroon
NMyC National Muslim Youth Camp
NMyC National Muslim Youth of Chicago
NMyC National Mycenaean
NMyC Naples Model Yacht Club
NMyC Northwest Marine Yacht Club
N-Myc NMyc
V-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian),
also known as MYCN, is a human gene.
This gene is a member of the MYC family and encodes a protein with a basic
helix-loop-helix (bHLH) domain. This protein is located in the nucleus and must
dimerize with another bHLH protein in order to bind DNA. Amplification of this
gene is associated with a variety of tumors, most notably neuroblastomas.
Myc (cMyc) is a protooncogene, which is overexpressed in a wide range of human
cancers. When it is specifically-mutated, or overexpressed, it increases cell
proliferation and functions as an oncogene. Myc gene encodes for a transcription
factor that regulates expression of 15% of all genes through binding on Enhancer
Box sequences (E-boxes) and recruiting histone acetyltransferases (HATs). Myc
belongs to Myc family of transcription factors, which also includes N-Myc and L-Myc
genes. Myc-family transcription factors contain the bHLH/LZ (basic
Helix-Loop-Helix Leucine Zipper) domain.
Discovery
Myc gene was first discovered in Burkitt's lymphoma patients. In Burkitt's
lymphoma, cancer cells show chromosomal translocations, in which Chromosome 8 is
frequently involved. Cloning the break point of the fusion chromosomes revealed
a gene that was similar to myelocytomatosis viral oncogene (v-Myc). Thus, the
new found cellular gene was named c-Myc.
Structure
Myc belongs to Myc family of transcription factors, which also includes N-Myc
and L-Myc genes. Myc family of transcription factors contain bHLH/LZ (basic
Helix-Loop-Helix Leucine Zipper) domain. Myc protein, through its bHLH domain
can bind to DNA, while the leucine zipper domain allows the dimerisation with
its partner Max, another bHLH transcription factor.
Molecular Function
Myc protein is a transcription factor that activates expression of a great
number of genes through binding on consensus sequences (Enhancer Box sequences
(E-boxes)) and recruiting histone acetyltransferases (HATs). It can also act as
a transcriptional repressor. By binding Miz-1 transcription factor and
displacing the p300 co-activator, it inhibits expression of Miz-1 target genes.
Myc is activated upon various mitogenic signals such as Wnt, Shh and EGF (via
the MAPK/ERK pathway). By modifying the expression of its target genes, Myc
activation results in numerous biological effects. The first to be discovered
was its capability to drive cell proliferation (upregulates cyclins,
downregulates p21), but it also plays a very important role in regulating cell
growth (upregulates ribosomal RNA and proteins), apoptosis (upregulates Bcl-2),
differentiation and stem cell self-renewal. Myc is a very strong proto-oncogene
and it is very often found to be upregulated in many types of cancers.
Animal Models
During the discovery of Myc gene, it was realized that chromosomes that
translocate to Chromosome 8 contained immunoglobulin genes at the break point.
Enhancers that normally drive expression of immunoglobin genes, now lead to
overexpression of Myc proto-oncogene in lymphoma cells. To study the mechanism
of tumorigenesis in Burkitt's lymphoma by mimicking expression pattern of Myc in
these cancer cells, transgenic mouse models were developed. Myc gene placed
under the control of IgM heavy chain enhancer in transgenic mice gives rise to
mainly lymphomas. Later on, to study effects of Myc in other types of cancer,
transgenic mice that overexpress Myc in different tissues (liver, breast) were
also made. In all these mouse models overexpression of Myc causes tumorigenesis,
illustrating the potency of Myc oncogene.
References
1. ^ Gearhart J, Pashos EE, Prasad MK, Pluripotency Redeux -- advances in
stem-cell researcg, N Engl J Med 357(15):1469
Further reading
* Ruf IK, Rhyne PW, Yang H, et al. (2002). "EBV regulates c-MYC, apoptosis, and
tumorigenicity in Burkitt's lymphoma.". Curr. Top. Microbiol. Immunol. 258:
153-60. PMID 11443860.
* Lüscher B (2001). "Function and regulation of the transcription factors of the
Myc/Max/Mad network.". Gene 277 (1-2): 1-14. PMID 11602341.
* Hoffman B, Amanullah A, Shafarenko M, Liebermann DA (2002). "The
proto-oncogene c-myc in hematopoietic development and leukemogenesis.". Oncogene
21 (21): 3414-21. DOI:10.1038/sj.onc.1205400. PMID 12032779.
* Pelengaris S, Khan M, Evan G (2002). "c-MYC: more than just a matter of life
and death.". Nat. Rev. Cancer 2 (10): 764-76. DOI:10.1038/nrc904. PMID 12360279.
* Nilsson JA, Cleveland JL (2004). "Myc pathways provoking cell suicide and
cancer.". Oncogene 22 (56): 9007-21. DOI:10.1038/sj.onc.1207261. PMID 14663479.
* Dang CV, O'donnell KA, Juopperi T (2005). "The great MYC escape in
tumorigenesis.". Cancer Cell 8 (3): 177-8. DOI:10.1016/j.ccr.2005.08.005. PMID
16169462.
* Dang CV, Li F, Lee LA (2007). "Could MYC induction of mitochondrial biogenesis
be linked to ROS production and genomic instability?". Cell Cycle 4 (11):
1465-6. PMID 16205115
Further reading
* Lüscher B (2001). "Function and regulation of the transcription factors of the
Myc/Max/Mad network.". Gene 277 (1-2): 1-14. PMID 11602341.
* Armstrong BC, Krystal GW (1992). "Isolation and characterization of
complementary DNA for N-cym, a gene encoded by the DNA strand opposite to N-myc.".
Cell Growth Differ. 3 (6): 385-90. PMID 1419902.
* Hagiwara T, Nakaya K, Nakamura Y, et al. (1992). "Specific phosphorylation of
the acidic central region of the N-myc protein by casein kinase II.". Eur. J.
Biochem. 209 (3): 945-50. PMID 1425701.
* Fougerousse F, Meloni R, Roudaut C, Beckmann JS (1992). "Dinucleotide repeat
polymorphism at the human hemoglobin alpha-1 pseudo-gene (HBAP1).". Nucleic
Acids Res. 20 (5): 1165. PMID 1549498.
* Krystal GW, Armstrong BC, Battey JF (1990). "N-myc mRNA forms an RNA-RNA
duplex with endogenous antisense transcripts.". Mol. Cell. Biol. 10 (8):
4180-91. PMID 1695323.
* Blackwood EM, Eisenman RN (1991). "Max: a helix-loop-helix zipper protein that
forms a sequence-specific DNA-binding complex with Myc.". Science 251 (4998):
1211-7. PMID 2006410.
* Emanuel BS, Balaban G, Boyd JP, et al. (1985). "N-myc amplification in
multiple homogeneously staining regions in two human neuroblastomas.". Proc.
Natl. Acad. Sci. U.S.A. 82 (11): 3736-40. PMID 2582423.
* Ibson JM, Rabbitts PH (1988). "Sequence of a germ-line N-myc gene and
amplification as a mechanism of activation.". Oncogene 2 (4): 399-402. PMID
2834684.
* Stanton LW, Schwab M, Bishop JM (1986). "Nucleotide sequence of the human N-myc
gene.". Proc. Natl. Acad. Sci. U.S.A. 83 (6): 1772-6. PMID 2869488.
* Michitsch RW, Melera PW (1985). "Nucleotide sequence of the 3' exon of the
human N-myc gene.". Nucleic Acids Res. 13 (7): 2545-58. PMID 2987858.
* Slamon DJ, Boone TC, Seeger RC, et al. (1986). "Identification and
characterization of the protein encoded by the human N-myc oncogene.". Science
232 (4751): 768-72. PMID 3008339.
* Garson JA, van den Berghe JA, Kemshead JT (1987). "Novel non-isotopic in situ
hybridization technique detects small (1 Kb) unique sequences in routinely
G-banded human chromosomes: fine mapping of N-myc and beta-NGF genes.". Nucleic
Acids Res. 15 (12): 4761-70. PMID 3299258.
* Stanton LW, Bishop JM (1988). "Alternative processing of RNA transcribed from
NMYC.". Mol. Cell. Biol. 7 (12): 4266-72. PMID 3437890.
* Kohl NE, Legouy E, DePinho RA, et al. (1986). "Human N-myc is closely related
in organization and nucleotide sequence to c-myc.". Nature 319 (6048): 73-7.
doi:10.1038/319073a0. PMID 3510398.
* Grady EF, Schwab M, Rosenau W (1987). "Expression of N-myc and c-src during
the development of fetal human brain.". Cancer Res. 47 (11): 2931-6. PMID
3552210.
* Ramsay G, Stanton L, Schwab M, Bishop JM (1987). "Human proto-oncogene N-myc
encodes nuclear proteins that bind DNA.". Mol. Cell. Biol. 6 (12): 4450-7. PMID
3796607.
* Brodeur GM, Seeger RC (1986). "Gene amplification in human neuroblastomas:
basic mechanisms and clinical implications.". Cancer Genet. Cytogenet. 19 (1-2):
101-11. PMID 3940169.
* Kanda N, Schreck R, Alt F, et al. (1983). "Isolation of amplified DNA
sequences from IMR-32 human neuroblastoma cells: facilitation by
fluorescence-activated flow sorting of metaphase chromosomes.". Proc. Natl.
Acad. Sci. U.S.A. 80 (13): 4069-73. PMID 6575396.
* Schwab M, Varmus HE, Bishop JM, et al. (1984). "Chromosome localization in
normal human cells and neuroblastomas of a gene related to c-myc.". Nature 308
(5956): 288-91. PMID 6700732.
* Brodeur GM, Seeger RC, Schwab M, et al. (1984). "Amplification of N-myc in
untreated human neuroblastomas correlates with advanced disease stage.". Science
224 (4653): 1121-4. PMID 6719137.
NMYC National Manpower and Youth Council
National Manpower and Youth Council; Composition. To carry out the objectives of
this Title, the National Manpower and Youth Council, which is attached to the
Department of Labor for policy and program coordination and hereinafter referred
to as the Council, shall be composed of the Secretary of Labor as ex-officio
chairman, the Secretary of Education and Culture as ex-officio vice-chairman,
and as ex-officio members, the Secretary of Economic Planning, the Secretary of
Natural Resources, the Chairman of the Civil Service Commission, the Secretary
of Social Welfare, the Secretary of Local Government, the Secretary of Science
and Technology, the Secretary of Trade and Industry and the Director-General of
the Council. The Director General shall have no vote.
In addition, the President shall appoint the following members from the private
sector: two (2) representatives of national organizations of employers; two (2)
representatives of national workers’ organizations; and one representative of
national family and youth organizations, each for a term of three (3) years.
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